Mitochondrial genomes are very stable

[Monique]

I was always thinking that the mitochondrial genomes are very stable, but now I am reading that they have an unusually high rate of mutation, which may contribute to many of the medical problems of old age.

So which is true maybe it's that mitochondria are passed down from mother to child, and that female germline cells go through a minimum of divisions and are metabolically inert, thus the mitochondria that are passed down the generation ARE stable? And they thus CAN have a high mutation rate..

 

[Monique]

For those who don't know, about one billion year a bacterium invaded a eukaryotic cell (animal) and formed a symbiotic relationship with it. That bacterium evolved into our energy producing machinery, the mitochondrion.

Evidence for that invasion are the double membrane of the organelle and the genetic code, which is similar to prokaryotes (bacteria) and not to eukaryotes (animals).

The chloroplast in plants has the same type of origin, only appeared later and thus shows more resemblence to the the original bacterium.

 

[Chemicalsuperfreak]

Had a biochem. prof tell me that most proteins in a mitochondria are actually encoded in nuclear DNA. The mitochondrial DNA only encodes something like 16 proteins, not nearly enough. So I'd guess mitochondria are subject to just as much mutation as we are.

 

[Monique]

Well, the genes in the nuclear DNA that code for mitochondrial proteins actually are of prokaryotic origin, but that on the side.

Directly from my textbook:
"Comparisons of DNA sequences in differtn organisms reveal that the rate of nucleotide substitutions during evolution has been 10 times greater in mitochondrial genomes than in nuclear genomes, which presumably is due to a reduced fidelity of mDNA replication, inefficient DNA repari, or both."

"Because only about 16500 DNA nucleotides need to be replicated and expressed as RNAs and proteins in animal cell mitochondria, the error rate per nucleotide copied by DNA replication, maintained by DNA repair, transcribed by RNA polymerases, or translated into protein by mitochondrial ribosomes can be relatively high without damaging one of the relatively few gene products."

"The relatively high rate of evolution of mitochondrial genes makes a comparison of mDNA sequences especially usefull for estimating the dates of relatively evolutionary events, such as the steps in primate evolution."

So what had been in MY mind the past years is that we were able to trace back our own ancestry to 7 or so Eves, due to the fact that mDNA is well conserved. Apparently the mutation rate is still comparitively high to nuclear DNA..

 

[Monique]

The human mitochondrial genome encodes 13 proteins, the largest is 97 genes in Reclinomonas americana.

 

[mark1]

why are mitochondria only passed on through the mother? i once heard an explanation for this that mitochondria are coded for on the X chromosome, which comes from the mother. this is a good explanation for men, who have an X chromosome from the mother and a Y chromosome from the father, but a woman, who has two X chromosomes from each parent, why can't she inherit the mitochondria from the X chromosome of the father?

 

[Monique]

Hi Mark1, you are confusing the X chromosome story with diseases that are linked to genes on that chromosome. Males ALWAYS inherit the X-chromosome from their mother and an Y chromosome from their father (the father doesn't pass on an X-chrom to his son).

In this case the mitochondria all come from the mother, because they are organelles that float in the cytoplasm. An egg cell is large and contains about 2000 mitochondria. A sperm is really very small compared to that, and the mitochondria are all located in its tale. When the sperm fertilizes the egg, the head fuses with the membrane, but leaves the tail behind. So that is why the sperm in doesn't contribute any mitochondria (although I have heard of some data, where a VERY small amount of DNA WAS found back from the father..).

 

[nautica]

It seems to me that you are confusing mutation rate with stability. Once a person has died, the mitochondrial DNA can be used for identification purposes, long after death, due to the high stability of the mitochondrial DNA. This has nothing to do with mutation rate, b/c mutations only occur in replication.

Nautica

 

[Monique]

But mitochondrial DNA is used to trace ancestries, it has been used to trace the geographic location from which humans originated, we are supposed to have decended from 7 different mothers, Eve's.

Mitochondrial DNA is not used for identification purposes, you have the same mDNA as all your siblings and your mother and your grantmother.

 

[nautica]

Mitochondrial DNA is used all the time in forensics. Obviously it can not set you apart from siblings, but it can tie it down pretty close.

Nautica

 

[Monique]

I really don't think so, the chromosome is only very small, what is the likelyhood going to be that it is the same to others? And since it is only passed down through mothers, and you would follow the passage of the chromosome from a grantgrantgrantmother through all the daughters, the familyweb that carry the same chromosome would be quite large..

You have any evidence to support your claim? As far as I know a collection of SNPs is used to identify people.

Why is mitochondrial DNA more stabile than genomic DNA?

 

[nautica]

http://www.mitotyping.com/dna.htm

 

[tyroman]

Swim Lessons?

A question form a novice:

Since the off-spring carries NO mDNA from the father, where is the evolutionary feedback/pressure which rewards the successful reproductive efforts of the organelles in the father's sperm?

In other words; "survival of the fittest" relies upon the passing on of successful mutations when they occur and yet such performance enhancing mutations as may have occurred in a SPERM's organelles which allowed it to sucessfully join with an egg, are lost to subsequent generations.

Note: the organelles in a sperm are the principal source of energy which the sperm uses to swim... swimming is something unique to sperm among all (higher life-form) eukaryotic cells... How did the sperm learn to swim?

Any theories?

 

[Monique]

Originally posted by tyroman
How did the sperm learn to swim?

Any theories?

VERY interesting question.. need to think about that one for a while :)

I don't know why you say the following though:

In other words; "survival of the fittest" relies upon the passing on of successful mutations when they occur and yet such performance enhancing mutations as may have occurred in a SPERM's organelles which allowed it to sucessfully join with an egg, are lost to subsequent generations.

Since only sperm which swim the fastest (and in the right direction) will pass on their DNA, their IS survival of the fittest and passing on of genes. What I wonder though at the moment.. are the mitochondria genes on the autosomes or on the X chromosome? Does that even matter?

 

[tyroman]

As to your observation vis a vis "survival of the fittest";

____________________________
Since only sperm which swim the fastest (and in the right direction) will pass on their DNA, their IS survival of the fittest and passing on of genes.
____________________________

My reference was to the (non) passing on of performance enhancing mutations in the sperm's organelles (mDNA) not to the sucessful nDNA propagation.

I guess the assumption is that the "motor" (organelle) is more important to a sperm's success than the "brain" (nucleus).

On the other issue you raise;

_____________________________
What I wonder though at the moment.. are the mitochondria genes on the autosomes or on the X chromosome? Does that even matter?
_____________________________

Not sure... aren't the mitochondrial genes in the organelles, not the nucleus?

 

[Monique]

Originally posted by tyroman
Not sure... aren't the mitochondrial genes in the organelles, not the nucleus?

Some time during evolution there was a transfer of mitochrial genes to the nuclear DNA, so part of them reside there. At some point this transfer stopped, not sure why.

 

[Monique]

My textbook says that the nucleus has to provide at least 90 genes just to maintain the organelle's genetic system. The diversity in the location of the genes coding for the subunits of functionally equivalent proteins in different organisms is difficult to explain by any hypothesis that postulates a specific evolutionary advantage of present-day mitochondrial or chloroplast genetic systems.

Perhaps the organelle genetic systems are an evolutionary dead-end. In terms of the endosymbiont hypothesis, this would mean that the process whereby the endosymbionts transferred most of their genes to the nucleus stopped before it was complete.

Further transfers may have been ruled out, for the mitochondria, by recent alterations in the mitochondrial genetic code that made the remaining mitochondrial genes nonfunctional if they were transferred to the nucleus.

From Alberts et al, molecular biology of the cell.

 

[tyroman]

As I understood it, the gene transfer was an "efficiency move" to eliminate redundancies and occurred relatively soon after the symbiosis event. It seems logical that if the same cellular function could be performed by two genes (one in the nucleus and one in the organelle) that a transfer of that job would occur under evolutionary pressures and that the larger, more complex nDNA's gene
would get the job (sort of like in some company mergers today).

Yet, your quote seems to imply an actual physical migration of genes from the mDNA into the nDNA... not an atrophy. Is there evidence of movement in the other direction... genes in the present mDNA which perform jobs originally done by genes in the nDNA (aside from the obvious next-step in metabolism)?

As it relates to the swim lesson question, the fact remains that the organelles perform the necessary cellular function of metabolism and that swimming requires efficient metabolism... do you agree?

To the extent that efficient metabolism in the organelles is governed by genes in the nDNA I agree that mutations in those genes DO get passed on as a reward for superior swimming... but what about a mutation in the mDNA of a given sperm cell which enhanced its performance...

Quoting myself - new emphasis:
In other words; "survival of the fittest" relies upon the passing on of successful mutations when they occur and yet such performance enhancing mutations as may have occurred in a sperm's ORGANELLES which allowed it to sucessfully join with an egg, are lost to subsequent generations.

Do you understand now why I said the preceeding?

Oh, as to Whohooo! ... statistics! don't you love it

 

[jhirlo]

How did the sperm learn to swim?

Huh it's not our sperm that learned to swim it's old evolutional characteristic existing from primordial animal life in water (same thing is with plants-just they reduced that characteristic with stepping from water ferns to larches )

 

[Monique]

Originally posted by tyroman
Yet, your quote seems to imply an actual physical migration of genes from the mDNA into the nDNA... not an atrophy. Is there evidence of movement in the other direction... genes in the present mDNA which perform jobs originally done by genes in the nDNA (aside from the obvious next-step in metabolism)?

Yes, the genes physically migrated from the mDNA to the nDNA. We know that because of their resemblence to bacterial genes and the existence of non-coding DNA sequences that seem to be of recent mitochondrial origin.

Quoting myself - new emphasis:
In other words; "survival of the fittest" relies upon the passing on of successful mutations when they occur and yet such performance enhancing mutations as may have occurred in a sperm's ORGANELLES which allowed it to sucessfully join with an egg, are lost to subsequent generations.

You are right for the genes encoded in the mDNA, which are 2 ribosomal RNAs, 22 transfer RNAs, and 13 different polypeptide chains. None of these will be passed on by the father to subsequent generations (although it is said that some portion of the sperm mDNA DOES get passed down).

But a fertilized egg has very high energy requirements, since it has to grow so fast, so there definitely IS an evolutionary feedback which selects for organisms with good functioning mitochondria. It is well documented that some females are infertile because of bad mitochondria in their eggs, and that cytoplasmic transfer from a healthy female overcomes the problem :)

Oh, as to Whohooo! ... statistics! don't you love it

:P did you get a chance to read it? I did my very best to make it readable for a non-initiated biology person, but that ain't easy ;)

 

[Monique]

Originally posted by jhirlo
Huh it's not our sperm that learned to swim it's old evolutional characteristic existing from primordial animal life in water (same thing is with plants-just they reduced that characteristic with stepping from water ferns to larches )

So where did the flagellum come from? Evolutionarily.. might there have been a different function for it before the sperm began using it. And which organisms have sperm in the shape as our?

 

[tyroman]

Eureka?

Sometimes, simply the act of asking a question gives the questioner insight into the answer...

Can the answer be right in front of us? Consider; the female implants one or a few eggs at a time while the male produces millions of sperm at each (attempted) reproductive event.

Lacking the evolutionary feedback/reinforcement of an mDNA link which might allow the male to reproduce his nDNA in an offspring with just one very smart, very speedy sperm cell; the male is reduced to spending the biological resources to send millions of very dumb, very slow sperm cells in order to improve the odds for reproduction.

Thus, the sperm never really "learn" (in an evolutionary sense) to swim as well as they might and evolution has compensated by producing many more sperm than might otherwise be necssary...

Is this the answer to my question?

 

[eagleone]

about flagellum evolution

Originally posted by Monique
So where did the flagellum come from? Evolutionarily.. might there have been a different function for it before the sperm began using it. And which organisms have sperm in the shape as our?

Of course that it had different function in the beginning, you can observe that even now at simple eukaryotic and prokaryotic unicellular organisms, and their usage of flagellum.
I’m thinking about it this way, evolution involving first unicellular life took them it two directions, or it’s better to say they had two strategies -> be bigger that others ; and make resources more accessible-your self less. From the first premise evolved multicellular life, and from second different differentiations allowing that organisms to move.

But as you probably know eukaryotic flagellum is different than prokaryotic one, and it could be easily convergence (though they do have similar parts). Many animals have mobile sex cells (invertebrates too), and many other non sexual cells have flagellums (that’s especially case with “lower ” animals), so you can't say that flagellum is strictly bonded with spermatozoids.

 

[Monique]

Yes, eucaryotic and procaryotic flagellums are different.. I am not so familiar with eucaryotic flagellums though, are they just an extention of the cell wall? Is it similar to pili in the gastrointestinal tract and the lungs?

 

[tyroman]

Monique,

Found the following statement fascinating;
__________________________________
It is well documented that some females are infertile because of bad mitochondria in their eggs, and that cytoplasmic transfer from a healthy female overcomes the problem :)
__________________________________

is it done by a.) first removing an egg's cytoplasm and all that it contains (reticula, ribosomes, mitochondria, etc.) and then inserting all the above from a healthy cell... or b.) just remove and replace the mitochondria... or c.) just inserting healthy mitochondria? Does the donor cell have to be an egg (or even necessarily female)?

This leads me to another question about mitochondria; do we know why evolution has selected to prevent male mDNA from entering the egg (and what happens if male mDNA is artificially injected into an egg nucleus?

As to;
__________________________________
:P did you get a chance to read it? I did my very best to make it readable for a non-initiated biology person, but that ain't easy ;)
__________________________________

Unfortunately, no. :( User ID and password were required when I tried to go to full text. Not a subscriber to Am. J. Hum. Genet.

Where is Center for Molecular Medicine and Genetics and are you still there?

Finally, what do you think of my hypothesis on the Swim Lesson question and how could it be tested?

 

[Monique]

Originally posted by tyroman
is it done by a.) first removing an egg's cytoplasm and all that it contains (reticula, ribosomes, mitochondria, etc.) and then inserting all the above from a healthy cell... or b.) just remove and replace the mitochondria... or c.) just inserting healthy mitochondria? Does the donor cell have to be an egg (or even necessarily female)?

It can be done by taking out the nucleus of the donor cell and placing in the nucleus of the patient or by microinjecting cytoplasm from the donor into the egg of the patient. A person born from that will have 3 genetic ancestors, recently there was a stirup where lesbian mother's were able to both become genetic mothers of a child, by cytoplasmic transfer. Unethical, since a disease is not cured or no problems overcome, but risks are being taken.

You ask a very interesting question -again :P- whether it need to by mitochondria from an egg. I think it should be, since the egg has its own biochemical program where there is a pool of nutrients in the cytoplasm. Another cell wouldn't have such nutrients and might thus not lead to proper fertilization.. but then again.. cloning has succesfully been attempted where an organism was born from ordinary cells :)

This leads me to another question about mitochondria; do we know why evolution has selected to prevent male mDNA from entering the egg (and what happens if male mDNA is artificially injected into an egg nucleus?

I don't know.. I'd have to know more about the actual chemical process that takes place when a sperm enters the egg. It might have something to do with the fact that an egg will make its plasmamembrane impenetrable once a single sperm breaks the surface (to prevent multiple fertilizations). Probably the tail with the mitochondria just gets stuck, while the head is able to dissolve.

Where is Center for Molecular Medicine and Genetics and are you still there?

No, I am no longer there, new challenges to be faced ;)

Finally, what do you think of my hypothesis on the Swim Lesson question and how could it be tested?

Um, so you said that sperm have no evolutionary feedback which allows them to perfect -or maintain- their mitochondrial function. Thus many sperms are made to compensate for bad function.

Hmm, I once watched a sample through a microscope in a hospital where they were doing diagnostic testing. That was a long time ago though, but my impression was that sperm normally are very good swimmers. What just came up in my head, is that there might be a reason why mitochondrial DNA moved to the nucleus! Evolutionary pressure to allow for sperm to pass along good genes, which allow them to swim well :) Sounds like a good hypothesis right? Why else would this transfer have occured?

Also, I mentioned that there is evolutionary pressure in the egg itself too after it is fertilized, passing on good mitochondria. Mitochondria are just energy power-houses, there are many more genes involved in the strategic placement of the mitochondria in the sperm along the actin(?) where energy is most needed. That won't be something encoded in the mDNA, rather in the nDNA.

I also remember you asking what would happen if sperm mitochondria were injected in the egg. Nothing really :) There are reports out there that claim they measured paternal mitochondrial DNA in offspring, up to 2% I believe.

Another interesting fact: sperm know in which direction to swim :D a long time ago a posted a thread (maybe I'll be able to find it) where there was a T-crossing and sperm had to choose which way to go. About 60% went in the direction where the egg was located :)

 

[eagleone]

Originally posted by Monique
Yes, eucaryotic and procaryotic flagellums are different.. I am not so familiar with eucaryotic flagellums though, are they just an extention of the cell wall? Is it similar to pili in the gastrointestinal tract and the lungs?

First no, second yes .
Pili of gastrointestinal cells are much simpler structures, you could say that they’re extensions of cell wall (membrane) backed up with microfilaments (actin skeleton). I’ve uploaded some pictures hope they’ll be helpful.

Gastrointestinal cell (pili and microfilaments)pic 1

In case of lung’s ciliar epitel you really do have cilia (active movable differentiations). Which is structurally same as spermatozoid’s flagellum or other eukaryotic flagellums. I’m not expert in field of comparative cytology, but I believe that you can find same structures at sexual and non sexual cells of other vertebrates and simpler animals (as I fogy remember from my zoology classes). Eukaryotic and spermatozoid’s flagellum is backed up with microtubule skeleton, it’s structure is called 9+2, because of number and disposition of microtubules:


Structure of eukaryotic flagellum (something from my old classes) : pic 2

Flagellum is attached to cell wall with actin, spectrin and miozin filaments. Junction places with membrane are most probably locations were the ion pumps are installed, (probably they’re on -< junctions (drawed as -< and >- on the pic)) . Were we come to the easies noticeable difference between pro end eukaryotic flagellum: eukaryotic is beating , and procaryiotic is rotating!

The prokaryotic f. it totally different, and unlike euc. It rotates (rather than beating). Prokaryotic flagella are long and thin, they are anchored at one end of membranes by a complex basal body. They are composed of protein flagellin, ad driven by complex flagellar motor.

Prokaryotic flagellum: pic 3

About "mitochondria discussion" - haven’t read all - too long - Although I more prefer that kind of discussion than this structural.

P.S. to administrator: you should enable code for all rooms except general discussion, because I believe you’ve disabled It just because of g. discussion.
[PLAIN] is useful, and if you enable it in that way, it want take you a lot of bandwidth, but it’ll help and increase quality of discussion.

p.s.s. pictures aren't available for now, FTP server is down[b(] , so I'll upload as son as they got FTP going ...

 

[eagleone]

server is barley up, nevertheless, pictures are up too...